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Acetylcholine modulation of neural systems involved in learning and memory.

Extensive evidence supports the view that cholinergic mechanisms modulate learning and memory formation. This paper reviews evidence for cholinergic regulation of multiple memory systems, noting that manipulations of cholinergic functions in many neural systems can enhance or impair memory for tasks generally associated with those neural systems. While parallel memory systems can be identified by combining lesions with carefully crafted tasks, most-if not all-tasks require the combinatorial participation of multiple neural systems. This paper offers the hypothesis that the magnitude of acetylcholine (ACh) release in different neural systems may regulate the relative contributions of these systems to learning. Recent studies of ACh release, obtained with in vivo microdialysis samples during training, together with direct injections of cholinergic drugs into different neural systems, provide evidence that release of ACh is important in engaging these systems during learning, and that the extent to which the systems are engaged is associated with individual differences in learning and memory.

Amygdala↗

The level of cholinergic nucleus basalis activation controls the specificity of auditory associative memory.

Learning involves not only the establishment of memory per se, but also the specific details of its contents. In classical conditioning, the former concerns whether an association was learned while the latter discloses what was learned. The neural bases of associativity have been studied extensively while neural mechanisms of memory specificity have been neglected. Stimulation of the cholinergic nucleus basalis (NBs) paired with a preceding tone induces CS-specific associative memory. As different levels of acetylcholine may be released naturally during different learning situations, we asked whether the level of activation of the cholinergic neuromodulatory system can control the degree of detail that is encoded and retrieved. Adult male rats were tested pre- and post-training for behavioral responses (interruption of ongoing respiration) to tones of various frequencies (1-15 kHz, 70 dB, 2 s). Training consisted of 200 trials/day of tone (8.0 kHz, 70 dB, 2 s) either paired or unpaired with NBs (CS-NBs = 1.8 s) at moderate (65.7+/-9.0 microA, one day) or weak (46.7+/-12.1 microA, three training days) levels of stimulation, under conditions of controlled behavioral state (pre-trial stable respiration rate). Post-training (24 h) responses to tones revealed that moderate activation induced both associative and CS-specific behavioral memory, whereas weak activation produced associative memory lacking frequency specificity. The degree of memory specificity 24 h after training was positively correlated with the magnitude of CS-elicited increase in gamma activity within the EEG during training, but only in the moderate NBs group. Thus, a low level of acetylcholine released by the nucleus basalis during learning is sufficient to induce associativity whereas a higher level of release enables the storage of greater experiential detail. gamma waves, which are thought to reflect the coordinated activity of cortical cells, appear to index the encoding of CS detail. The findings demonstrate that the amount of detail in memory can be directly controlled by neural intervention.

Animals↗

Learning and memory in monozygotic twins discordant for schizophrenia.

Learning and memory were assessed in 24 monozygotic (MZ) pairs of individuals discordant for schizophrenia or delusional disorder and seven normal pairs of MZ twins. On declarative memory tasks, the affected group displayed a pattern that might best be characterized as dysmnesic in that they performed significantly worse than the discordant unaffected group on story recall, paired associated learning, and visual recall of designs, but they learned over time, had relatively preserved recognition memory, and did not show profoundly accelerated rates of forgetting. Effortful, volitional retrieval from the lexicon, measured by verbal fluency, was also compromised in the affected group. On the other hand, procedural learning of the motor skill in a pursuit rotor task was relatively intact in the affected group. Comparisons of the normal group and unaffected group indicated that the latter group had very mild impairments in some aspects of episodic memory, namely, immediate and delayed recall of stories and delayed recall of designs. It is highly unlikely that the impairments observed in the affected group can be attributed to differences in genome, family environment, socioeconomic circumstance, or educational opportunity, as all of these were controlled by the twin paradigm. Rather, the impairments appear to be related to the intercession of disease. The neuropsychological profile is consistent with frontal lobe and medial temporal lobe dysfunction, as noted in this sample as well as other samples of schizophrenic singletons. Significant correlations between many measures of memory and global level of social and vocational functioning within the discordant group were also found. Thus difficulties in rapidly acquiring new information and propitiously retrieving old information may burden patients with schizophrenia in many of the transactions of everyday life.

Adolescent↗

[Relationships between learning and memory and expression of nov gene of rats].

During the establishment of learning and memory of adult rats with active avoidance reaction expression of nov gene, nov mRNA positive neurons and NOV protein immunoreactive neurons were found in hippocampus, cingulate cortex, globus pallidus, caudate putamen and hypothalamus. The strongest positive reaction of NOV protein was observed in high ability group of learning and memory (HALM). Basic expression was found in pseudoconditioning (PC) group. The expression of NOV protein was higher in low ability group of learning and memory (LALM) than in PC group. No significant difference was detected in nov mRNA positive reaction between the three groups. The results indicate that nov gene may play an important role in learning and memory of adult rats. This regulation occurs at the level of NOV protein translation.

Animals↗

Memories that last in old age: motor skill learning and memory preservation.

Using an automated test panel, age-associated declines in learning, remembering and performing a novel visuomotor task were assessed in 497 normal adults ranging from 18 to 95 years old. As predicted, task performance times slowed with increasing age in the cross-sectional portion of the study. However in the subsequent longitudinal study, while motor learning was significantly slower in adults over 62 years old, motor memory was pristinely preserved in normal adults from 18 to 95 years old. When tested 2 years after the first training session and without intervening rehearsal, mean performance times were retained and continued to improve by 10% in young adults and 13% in aged adults, reflecting long lasting preservation of motor memories. While the maximum lifetime of an unpracticed, novel motor memory in humans is not known, the present study suggests that new motor memories can be retained for at least 2 years without rehearsal in normal aged adults. This age-resistant component of motor memory stands in contrast to the well-known decrements in other motor and cognitive processes with human aging.

Adolescent↗

Age-related decline in spatial learning and memory: attenuation by captopril.

Spontaneously hypertensive rats (SHR) compared to normotensive rats display an accelerated decline in spatial learning and memory. However, few studies have systematically examined the independent contribution of hypertension vs. other age-related mechanisms to this decline. The present study uses a repeated acquisition water maze task to test the hypothesis that hypertension and/or the presence of angiotensin II can accelerate the age-related decrease of spatial learning and memory in rats. We have previously shown that both SHR and Wistar-Kyoto rats (WKY) display age-related decreases in spatial learning and memory; however, the rate of decline differs between the strains. The present results demonstrate that compared to young rats of the same strain, learning and memory in SHR declines significantly already at 12 months of age, and at 24 months of age both SHR and WKY rats are severely impaired in the water maze task. Lifetime treatment of either SHR or WKY with the antihypertensive drug captopril [an angiotensin converting enzyme (ACE) inhibitor] significantly attenuates the age-related impairment in learning and memory. In contrast, chronic treatment of SHR with captopril from 6 months of age only modestly decreases the decline in learning and memory. Whereas lifetime treatment with the vasodilator drug hydralazine also reduces arterial pressure in SHR, this treatment does not significantly preserve learning in 24-month-old SHR. Together, the data suggest captopril can delay the decline in spatial learning and memory in both aging SHR and WKY. Further, the results indicate that the memory enhancing effects of captopril are not primarily the due to the ability of captopril to lower blood pressure.

Aging↗

Delaying judgments of learning affects memory, not metamemory.

Judgments of learning (JOLs) for cue-target word pairs correlate particularly well with later target recall when made under conditions that permit delayed attempts to retrieve the targets--the delayed-JOL effect. Metamemory theories claim that memory monitoring improves under these conditions. However, another theory--the memory hypothesis--claims that the correlation increases because retrieved items receive a boost in recall from spaced study and are assigned high JOLs, whereas unretrieved items receive no spaced study and, therefore, no boost in recall and, consequently, are assigned low JOLs. When we eliminated differences in spaced study by reexposing word pairs following their JOLs, the delayed-JOL effect disappeared, supporting the memory hypothesis.

Cues↗

The role of sleep in learning and memory.

Sleep has been implicated in the plastic cerebral changes that underlie learning and memory. Indications that sleep participates in the consolidation of fresh memory traces come from a wide range of experimental observations. At the network level, reactivations during sleep of neuronal assemblies recently challenged by new environmental circumstances have been reported in different experimental designs. These neuronal assemblies are proposed to be involved in the processing of memory traces during sleep. However, despite this rapidly growing body of experimental data, evidence for the influence of sleep discharge patterns on memory traces remains fragmentary. The underlying role of sleep in learning and memory has yet to be precisely characterized.

Animals↗

[Effects of marginal vitamin A deficiency and intervention on learning and memory in young rats].

OBJECTIVE: Previous studies have demonstrated that vitamin A and its active derivatives function as essential competence factors for long-term synaptic plasticity within the adult brain. But little is known if marginal vitamin A deficiency (MVAD) beginning from embryonic period affects the brain development and the ability of learning and memory in young rats. The aim of this study was to identify the effects of MVAD and vitamin A intervention (VAI) on learning, memory and the hippocampal CA1 long-term potentiation (LTP) in young rats. METHODS: Rats were divided into control, MVAD and VAI groups in this study. In control group (10 young rats) the dams and pups were fed with normal diet (VA 6500 IU/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD diet (VA 400 IU/kg). In VAI group (9 young rats) the dams were fed with MVAD diet and the pups were fed with normal diet from postnatal week 4. All the young rats were killed at the age of 7 weeks. During the last week of the experiment, the shuttle box active avoidance reaction tests were carried out. At week 7, the hippocampal CA1 LTP was detected by electrophysiological technique and relative intensity of fluorescence in cells in hippocampal slices was measured by confocal laser scanning microscopy labeled by fluo-3. RESULTS: (1) The times to reach the learning standard in both VAI group (28.8 +/- 4.1) and MVAD group (45.6 +/- 12.1) were more than control group (17.1 +/- 4.4) (P < 0.01), and that of MVAD group was more than VAI group (P < 0.05) in active avoidance reaction tests. (2) The changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group (22.9% +/- 9.4%) and VAI group (29.5% +/- 13.7%) were less than that of control group (57.5% +/- 27.3%), respectively (P < 0.01). No significant difference was found between VAI and MVAD groups (P > 0.05). (3) No significant differences of relative intensity of fluorescence in cells were found among the three groups before the tetanus stimulation. However, the significantly low relative intensity of fluorescence in cells was seen in MVAD (65.1 +/- 17.0) and VAI (85.8 +/- 17.1) groups compared with control group (113.6 +/- 20.5) after the tetanus stimulation (P < 0.01), and that of VAI group was higher than that of MVAD group (P < 0.05). CONCLUSION: MVAD beginning from embryonic period impairs learning, memory and LTP in young rats. But the losses might not be reversible if the vitamin A supplementation is late especially missing the critical period of hippocampus development. According to the experimental data, it is speculated that vitamin A may modulate the influx of calcium ion to influence the LTP and lead to the change of learning and memory.

Animals↗

Neural cell adhesion molecules, learning, and memory in the domestic chick.

The intermediate and medial hyperstriatum ventrale (IMHV) of the chick forebrain is a site of recognition memory for the learning process of imprinting. The results reported here demonstrate that neural cell adhesion molecules (NCAMs) play a time-dependent role in this recognition memory. Dark-reared chicks were trained, tested, and assigned a preference score as a measure of learning. Chicks with high preference scores were designated good learners and those with lower preference scores, poor learners. Controls were untrained. Tissue was removed, 9.5 hr or 24 hr after training, from the left and right IMHV, hyperstriatum accessorium, and posterior neostriatum. Three major NCAM isoforms (180, 140, and 120 kDa) were assayed. At 24 hr only, there was in left IMHV significantly more NCAM (for each isoform) in good learners than in the other 2 groups, and also a significant correlation between the amounts of NCAM and preference scores for all isoforms; the amount predicted by each regression line at preference score 50 (no learning) did not differ significantly from the mean value for untrained controls. There were no learning-related effects in either the hyperstriatum accessorium or the posterior neostriatum.

Analysis of Variance↗

Learning and memory in honeybees: from behavior to neural substrates.

Learning and memory in honeybees is analyzed on five levels, using a top-down approach. (a) Observatory learning is applied during navigation and dance communication. (b) Local cues at the feeding site are learned associatively. (c) Classical conditioning of the proboscis extension response to olfactory stimuli provides insight into behavioral, neural, and neuropharmacological mechanisms of associative learning. (d) At the neural level, the pathways coding the conditioned and the unconditioned stimulus are identified. The reinforcing function of the unconditioned stimulus is traced to a particular neuron. (e) At the cellular level, the cAMP pathway is found to be critically involved. Nitric oxide is an essential mediator for the transfer from short- to long-term memory.

Animal Communication↗

Cortisol, contingency learning, and memory in preterm and full-term infants.

Cortisol plays an important role in learning and memory. An inverted-U shaped function has been proposed to account for the positive and negative effects of cortisol on cognitive performance and memory in adults, such that too little or too much impair but moderate amounts facilitate performance. Whether such relationships between cortisol and mental function apply to early infancy, when cortisol secretion, learning, and memory undergo rapid developmental changes, is unknown. We compared relationships between learning/memory and cortisol in preterm and full-term infants and examined whether a greater risk for adrenal insufficiency associated with prematurity produces differential cortisol-memory relationships. Learning in three-month old (corrected for gestational age) preterm and full-term infants was evaluated using a conjugate reinforcement mobile task. Memory was tested by repeating the same task 24h later. Salivary cortisol samples were collected before and 20 min after the presentation of the mobile. We found that preterm infants had lower cortisol levels and smaller cortisol responses than full-term infants. This is consistent with relative adrenal insufficiency reported in the neonatal period. Infants who showed increased cortisol levels from 0 to 20 min on Day 1 had significantly better memory, regardless of prematurity, than infants who showed decreased cortisol levels.

Female↗

Chronic ethanol consumption impairs learning and memory after cessation of ethanol.

Acute consumption of ethanol results in reversible changes in learning and memory whereas chronic ethanol consumption of six or more months produces permanent deficits and neural damage in rodents. The goal of the current paper was determine whether shorter durations of chronic ethanol ingestion in mice would produce long-term deficits in learning and memory after the cessation of ethanol. We first examined the effects of four and eight weeks of 20% ethanol followed by a three week withdrawal period on learning and memory in mice. We determined that three weeks after eight, but not four, weeks of 20% ethanol consumption resulted in deficits in learning and long-term memory (seven days) in T-maze footshock avoidance and Greek Cross brightness discrimination, step-down passive avoidance and shuttlebox active avoidance. Short-term memory (1 hr) was not affected. The deficit was not related to changes in thiamine status, caloric intake, or nonmnemonic factors, such as, activity or footshock sensitivity. Lastly, we examined if the mice recovered after longer durations of withdrawal. After eight weeks of ethanol, we compared mice after three and 12 weeks of withdrawal. Mice that had been off ethanol for both three and 12 weeks were impaired in T-maze footshock avoidance compared to the controls. The current results indicate that a duration of ethanol consumption as short as eight weeks produces deficits in learning and memory that are present 12 weeks after withdrawal.

Alcohol Drinking↗

[Progress on the study of neurochemical mechanisms of learning and memory].

Brain function research is one of the most important projects in biological sciences. Learning and memory is one of the most advanced functions in brain. This article reviewed the effects of some neurotransmitters and neuroactive peptides on learning and memory in an attempt to stimulate the research aiming at improving learning and memory.

Animals↗

Verbal and visuospatial learning and memory function in children with moderate prenatal alcohol exposure.

BACKGROUND: This study investigated the effects of moderate prenatal alcohol exposure on learning and memory in 14-year-old adolescents. The Children's Memory Scale was used to assess learning and memory function in the verbal/auditory and visual/spatial domains. In addition, both short- and long-term memory function were assessed. METHODS: Data were collected as part of the Maternal Health Practices and Child Development Project, a longitudinal study including 580 children and their mothers. Women were assessed during each trimester of pregnancy and with their children from birth to 16 years of age. At age 14, memory function was evaluated using the Children's Memory Scale, an assessment tool that measures learning and immediate and delayed memory function in the verbal and visual-spatial domains. RESULTS: Prenatal alcohol exposure during the first trimester predicted deficits in learning, short-term memory, and long-term memory, specifically in the verbal domain. Deficits in performance were specific to learning and memory of word-pairs. In addition, deficits in memory were mediated by learning performance. CONCLUSIONS: Results demonstrated that prenatal alcohol exposure lead to deficits in encoding processes as indicated by deficits in verbal learning. Initial deficits in acquisition were responsible for deficits in immediate and delayed recall of verbal information in children who were exposed to alcohol during pregnancy but did not have fetal alcohol syndrome.

Adolescent↗

Memory and learning in epileptic patients treated by amygdalotomy and anterior hippocampotomy.

The memory and learning capacity in patients treated for temporal epilepsy was studied. The study was performed in 55 patients, observed before and after stereotaxic amygdalotomy and hippocampotomy. Very often disturbances in memory and learning capability were present before surgery. After surgery their learning efficiency increased. Disturbances in memory tracing, as provoked by distraction, remained at the same level after neurosurgery. No decrease in general intelligence was noted.

Adolescent↗

[The neuroethological basis of learning and memory decline in aged rats].

The spatial reference and working memory abilities, GFAP-positive astrocytes and GABAergic interneurons were studied quantitatively in young, aged memory-unimpaired and aged memory-impaired rats according to their learning and memory abilities in the Morris water maze. The results showed that the prominent behavioural features of the aged memory-impaired rat were a change in the searching pattern, a decrease in the spatial reference memory, no significant decrease in the spatial working memory was observed. The decrease of GABAergic neurons, and the increase of GFAP-positive astrocytes in the dentate gyrus of the aged memory-impaired rat were more obvious than the other two groups. The main abnormalities of morphologic indexes were closely correlated with the decline of learning and memory in the aged rat.

Aging↗

Neuronal plasticity in the mammalian brain: relevance to behavioral learning and memory.

Much recent activity in the neurosciences relates to the search for the brain mechanisms underlying learning and memory. In recent years a brain circuit in cerebellum and brainstem has been discovered that is responsible for the learning of a simple motor response (nictitating membrane movement). This has provided a model for neuroscientists to use in understanding the brain circuits involved in this simple form of learning and, by extension, to more complex forms ultimately, and a means of exploring the changes in neural function underlying the learning. An enduring change in neural function is represented by long-term potentiation (LTP), an alteration in synaptic efficacy seen in hippocampus and other areas. LTP can be induced experimentally and occurs as a concomitant of learning. We review data suggesting that different brain circuits may underlie different forms of learning and memory. Several current theories of learning and memory with respect to hippocampal and other brain circuit involvement are considered. We conclude with the behavioral and physiological effects of exposure to teratogens or toxins and the CNS alterations associated with dementia.

Animals↗